The primary hypothesis of this grant is that chronic inflammation and apoptosis lead to hippocampusdependent behavioral deficits. There is accumulating evidence for the role of IL1b in learning and memory. In aged rats there is an increase in IL1b that has been implicated in declines of synaptic plasticity in the hippocampus and performance on cognitive tasks. There are several questions about the role of this cytokine in learning and memory processes that remain unanswered. 1) Are increased levels of IL-1 directly responsible for deficits in learning and memory occurring in normal age? 2) Is IL-1 presence at physiological levels in young rats a limiting-step in the acquisition and storage of memory? 3) and finally, which are the mechanisms by which IL-1 affects memory? Many elderly individuals exhibit deficits in learning and memory processes, as well as decreased numbers of neurons in different regions of the brain. However, the development of more accurate procedures for counting neurons, such as the use of stereology, has raised doubts about the decline in neurons number, via neuronal death during normal aging. If significant neuronal loss is lacking, several pathological features of neurodegeneration, such as the presence of Lewy bodies, typical of Parkinson's disease, and senile plaques, typical of Alzheimer's disease, can be detected in brains of aged individuals. So, the question that has been raised from these observations is whether or not apoptosis, beyond its involvement in neuronal death, affects the decline in cognitive processes occurring during normal aging. Caspases are a family of proteases that play a critical role in long-term spatial memory storage. Caspase-1 (IL-1b converting enzyme) has the peculiarity of being involved in the activation of both apoptosis and inflammation, through the intermediate of IL-1b. It has been shown that inhibition of caspase-1 induces neuroprotection in cerebral ischemia through apoptosis reduction and decrease of proirrflammatory cytokines. Although interleukin-1b is highly expressed in neurodegenerative disease, is involved in cognitive impairment, and induces cell death in glial cells cultures, whether IL-1b and caspase interact each other to express their effects on learning and memory, it is still unknown.